Analytical and clinical validation of PATHWAY Anti-HER-2/neu (4B5) antibody to assess HER2-low status for trastuzumab deruxtecan treatment in breast cancer.

In DESTINY-Breast04 (DB-04), safety and efficacy of HER2-targeted antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) in previously treated HER2-low unresectable/metastatic breast cancer were established. This manuscript describes the analytical validation of PATHWAY Anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody (PATHWAY HER2 (4B5)) to assess HER2-low status and its clinical performance in DB-04. Preanalytical processing and tissue staining parameters were evaluated to determine their impact on HER2 scoring. The recommended antibody staining procedure provided the optimal tumor staining, and deviations in cell conditioning and/or antibody incubation times resulted in unacceptable negative control staining and/or HER2-low status changes. Comparisons between antibody lots, kit lots, instruments, and day-to-day runs showed overall percent agreements (OPAs) exceeding 97.9%. Inter-laboratory reproducibility showed OPAs of ≥97.4% for all study endpoints. PATHWAY HER2 (4B5) was utilized in DB-04 for patient selection using 1340 tumor samples (59.0% metastatic, 40.7% primary, (0.3% missing data); 74.3% biopsy, 25.7% resection/excisions). Overall, 77.6% (823/1060) of samples were HER2-low by both central and local testing, with the level of concordance differing by sample region of origin and collection date. In DB-04, the efficacy of T-DXd over chemotherapy of physician's choice was consistent, regardless of the characteristics of the sample used (primary or metastatic, archival, or newly collected, biopsy or excision/resection). These results demonstrate that PATHWAY HER2 (4B5) is precise and reproducible for scoring HER2-low status and can be used with multiple breast cancer sample types for reliably identifying patients whose tumors have HER2-low expression and are likely to derive clinical benefit from T-DXd.

Impact of deforestation and temporal land-use change on soil organic carbon storage, quality, and lability.

Soil organic carbon (SOC) plays a key role in regulating soil quality functions and ecosystem services. The objective of our study was to evaluate the impact of deforestation and subsequent land-use change on the SOC and total nitrogen (TN) concentration, quality, and lability under otherwise similar soil and environmental conditions. Geo-referenced composite soils (0 to 30 cm depth at 7.5 cm interval) sampled from agriculture, bioenergy plantations (Miscanthus x giganteus), Conservation Reserve Program (CRP), and wetland were analyzed for SOC, TN, active C (AC), humic- and fulvic acid (HA and FA), non-humic C (NH), E4: E6 ratio, humification indices (HI, HR, and DH), and carbon and nitrogen management indices (CPI, NPI, and CMI), compared to soils under protected forest as a control. Results showed that the CRP had the highest depth distribution and profile-wise stocks of SOC, TN, AC, and FA with respect to the lowest in agriculture upon conversion of forest. Moreover, the SOC and TN contents were significantly stratified in the CRP when compared to agriculture. While agriculture had the wider HA: FA ratios with highest HI and HR but lowest DH values, the CRP, in contrast, had the narrow HA: FA ratios with lowest HI but highest DH values, when compared to the forest. Spectral analyses have shown lower E4: E6 ratios under the forest when compared to both agriculture and the CRP; however, the later had significantly higher E4: E6 ratios than that of agriculture. The CPI, as measures of SOC accumulation or depletion, significantly decreased by 16% under agriculture but increased by 12% under the CRP. While the CMI, as measures of SOC accumulation or depletion and lability, with higher values under the CRP suggested a proportionally more labile SOC accumulation, in contrast, the smaller values under agriculture indicated a greater depletion of labile SOC over time. Moreover, the CRP may have favored a more labile SOC accumulation with higher proportions of aliphatic C compounds, whereas agriculture may have a SOC with high proportions of non-labile aromatic C compounds. Principal components analysis clearly separated and/or discriminated the land-use impacts on soil carbon pools and TN. Likewise, redundancy analysis of the relationship between measured soil parameters and land-use validated that the TOC, TN, FA, humin, and CPI were significantly impacted due to synergism among soil properties as positively influenced by the CRP upon conversion of agriculture.

Assessing Transcendental Experiences vs Mental Illnesses.

In our experience, being able to differentiate between mental illness and transcendent experiences has led patients to remain engaged in treatment. This is important since those who have experienced religious preoccupation are the least likely to seek out mental health care. We have developed a "Transcendent Assessment Tool" to assist clinicians and clients in discerning whether an experience is a delusion or part of a transcendent experience.